HemoShear is a discovery stage biotechnology company that recreates human disease biology by combining human primary cells with fundamental principles of hemodynamic flow and biological transport to restore physiologically accurate human tissue biology, allowing the creation of disease conditions and study of risk factors and drugs at clinically-relevant concentrations. Current 2D tumor cell in vitro systems do not accurately predict efficacy or safety of anticancer therapies in humans. In vivo mouse models have significant limitations and historically have a poor correlation with human clinical outcomes. Under the NCI 314 Phase I contract, HemoShear developed a proof-of-principle multi-cellular non-small cell lung carcinoma 3D in vitro system that recreated tumor microenvironment biology and showed efficacious responses to clinical concentrations of FDA approved chemotherapeutics. The goal of this contract is to further validate the TMeS against known effective anti-cancer agents and to demonstrate the utility as a predictive tool or screening assay for drug discovery and development in cancer. Hemoshear will benchmark performance against applicable in vivo animal models and known clinical performance. Hemoshear will scale technology throughput while maintaining our high-content capabilities. The following tasks will achieve this: 1) Test diverse chemotherapeutics with known clinical profiles in the HemoShear TMeS. 2) Benchmark the ?omic profile of cancer cells grown in the HemoShear TMeS to in vivo xenografts. 3) Scale the TMeS throughput while maintaining high-content capabilities. 4) Use the higher throughput TMeS and high-content imaging to determine the dose-response relationship of FDA-approved chemotherapeutics.